Once-Weekly Subcutaneous Bortezomib Plus Oral Cyclophosphamide and Dexamethasone Therapy For Relapsed Or Refractory Multiple Myeloma

We previously reported that twice-weekly intravenous bortezomib plus doxorubicin and intermediate-dose dexamethasone (iPAD) therapy induced a high complete response (CR) rate of 30% and prolonged remission duration of median 12.1 months in patients with relapsed or refractory myeloma. However, sensory neuropathy was observed in 78% of the patients with grade 3 neuropathy in 22%. To reduce the toxicity, we conducted once-weekly subcutaneous bortezomib therapy given in combination with oral cyclophosphamide and dexamethasone (sVCD).

This was a phase 2 multicenter study conducted by the Kyushu Hematology Organization for Treatment Study Group (K-HOT). sVCD regimen consists of bortezomib 1.3 mg/m² administered subcutaneously, and cyclophosphamide 300 mg/m² and dexamethasone 40 mg given orally on days 1, 8, 15 and 22. The treatment was repeated at a 5-week interval for 6 cycles. The primary endpoint was to determine the complete response rate. The toxicities including sensory neuropathy and injection site reaction were analyzed as the secondary endpoint. The study was approved by the Institutional Review Board at each participating center and was registered in University hospital Medical Information Network (UMIN000006490). All patients provided a written-informed consent.

Thirty-one patients with median age of 69 (range, 43-87) were entered into this study. The numbers of prior chemotherapy line were 1 in 39%, 2 in 23%, and more than 3 in 39% of the patients. Bortezomib, lenalidomide and thalidomide had been given in 52%, 26% and 16%, respectively. CR was achieved in 16%, partial response (PR) in 26%, and minimal response (MR) in 29%, resulting in overall response rate of 71%. Grade 3/4 neutropenia was observed in 35%/3%, thrombocytopenia in 16%/13%, and anemia in 45%/0% of the patients. Grade 3 to 4 non-hematological toxicities were uncommon; the highest incidence of grade 3 events were rash, hyponatremia and hyperglycemia observed in 6%, while no grade 4 events were reported. Grade 3 sensory neuropathy developed in 3% and grade 2 in 19%. Injection site reactions were observed in 39%, but all of them were grade 1.

sVCD therapy containing bortezomib administered subcutaneously in once-weekly schedule successfully reduced the incidence and severity of sensory neuropathy with moderate response rate.

Miyamoto:Kyushu University Hospital: Employment.